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Diverse manifestations of biological aging often reflect disparities in socioeconomic status (SES). In this paper, we examine associations between indicators of SES and an mRNA-based aging signature during young adulthood, before clinical indications of aging are common. We use data from wave V (2016–2018) of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adults aged 33–43 years, with transcriptomic data from a subset of 2,491 participants. Biological aging is measured using 1) a composite transcriptomic aging signature previously identified by Peters et al.'s out-of-sample meta-analysis (Nat Commun. 2015;6:8570) and 2) 9 subsets that represent functional pathways of coexpressed genes. SES refers to income, education, occupation, subjective social status, and a composite measure combining these 4 dimensions. We examine hypothesized mechanisms through which SES could affect aging: body mass index, smoking, health insurance status, difficulty paying bills, and psychosocial stress. We find that SES—especially the composite measure and income—is associated with transcriptomic aging and immune, mitochondrial, ribosomal, lysosomal, and proteomal pathways. Counterfactual mediational models suggest that the mediators partially account for these associations. The results thus reveal that numerous biological pathways associated with aging are already linked to SES in young adulthood. [ABSTRACT FROM AUTHOR]

Principled methods with which to appropriately analyze missing data have long existed; however, broad implementation of these methods remains challenging. In this and 2 companion papers (Am J Epidemiol. 2018;187(3):576-584 and Am J Epidemiol. 2018;187(3):585-591), we discuss issues pertaining to missing data in the epidemiologic literature. We provide details regarding missing-data mechanisms and nomenclature and encourage the conduct of principled analyses through a detailed comparison of multiple imputation and inverse probability weighting. Data from the Collaborative Perinatal Project, a multisite US study conducted from 1959 to 1974, are used to create a masked data-analytical challenge with missing data induced by known mechanisms. We illustrate the deleterious effects of missing data with naive methods and show how principled methods can sometimes mitigate such effects. For example, when data were missing at random, naive methods showed a spurious protective effect of smoking on the risk of spontaneous abortion (odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.19, 0.93),while implementation of principled methods multiple imputation (OR = 1.30, 95% CI: 0.95, 1.77) or augmented inverse probability weighting (OR = 1.40, 95% CI: 1.00, 1.97) provided estimates closer to the "true" full-data effect (OR = 1.31, 95% CI: 1.05, 1.64). We call for greater acknowledgement of and attention to missing data and for the broad use of principled missing-data methods in epidemiologic research. [ABSTRACT FROM AUTHOR]

Missing data is a common occurrence in epidemiologic research. In this paper, 3 data sets with induced missing values from the Collaborative Perinatal Project, a multisite US study conducted from 1959 to 1974, are provided as examples of prototypical epidemiologic studies with missing data. Our goal was to estimate the association of maternal smoking behavior with spontaneous abortion while adjusting for numerous confounders. At the same time, we did not necessarily wish to evaluate the joint distribution among potentially unobserved covariates, which is seldom the subject of substantive scientific interest. The inverse probability weighting (IPW) approach preserves the semiparametric structure of the underlying model of substantive interest and clearly separates the model of substantive interest from the model used to account for the missing data. However, IPW often will not result in valid inference if the missing-data pattern is nonmonotone, even if the data are missing at random. We describe a recently proposed approach to modeling nonmonotone missing-data mechanisms under missingness at random to use in constructing the weights in IPW complete-case estimation, and we illustrate the approach using 3 data sets described in a companion article (AmJ Epidemiol. 2018;187(3):568-575). [ABSTRACT FROM AUTHOR]

Epidemiologic studies are frequently susceptible to missing information. Omitting observations with missing variables remains a common strategy in epidemiologic studies, yet this simple approach can often severely bias parameter estimates of interest if the values are not missing completely at random. Even when missingness is completely random, complete-case analysis can reduce the efficiency of estimated parameters, because large amounts of available data are simply tossed out with the incomplete observations. Alternative methods for mitigating the influence of missing information, such as multiple imputation, are becoming an increasing popular strategy in order to retain all available information, reduce potential bias, and improve efficiency in parameter estimation. In this paper, we describe the theoretical underpinnings of multiple imputation, and we illustrate application of this method as part of a collaborative challenge to assess the performance of various techniques for dealing with missing data (Am J Epidemiol. 2018;187(3):568-575 ). We detail the steps necessary to perform multiple imputation on a subset of data from the Collaborative Perinatal Project (1959-1974), where the goal is to estimate the odds of spontaneous abortion associated with smoking during pregnancy. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including emerging challenges for prison health, adverse effects of incarceration on families of prisoners, and the prevalence of treatable mental disorders.

Increasingly often in epidemiologic research, associations between survival time and predictors of interest are measured by differences between distribution functions rather than hazard functions. For example, differences in percentiles of survival time, expressed in absolute time units (e.g., weeks), may complement the popular risk ratios, which are unitless measures. When analyzing time to an event of interest (e.g., death) in prospective cohort studies, the time scale can be set to start at birth or at study entry. The advantages of one time origin over the other have been thoroughly explored for the estimation of risks but not for the estimation of survival percentiles. In this paper, we analyze the use of different time scales in the estimation of survival percentiles with Laplace regression. Using this regression method, investigators can estimate percentiles of survival time over levels of an exposure of interest while adjusting for potential confounders. Our findings may help to improve modeling strategies and ease interpretation in the estimation of survival percentiles in prospective cohort studies. [ABSTRACT FROM AUTHOR]

The authors conducted a meta-analysis of the association between smoking before a first pregnancy, when undifferentiated breast tissue may be vulnerable to tobacco carcinogens, and the risk of breast cancer. A search of the published literature through August 2010 identified 23 papers reporting on associations between smoking before a first pregnancy and breast cancer. Odds ratios or hazard ratios and 95% confidence intervals, adjusted for known or suspected breast cancer risk factors, were abstracted from each study. Data were pooled using both fixed- and random-effects models. The fixed-effect summary risk ratio for breast cancer among the women who smoked before their first pregnancy versus women who had never smoked was 1.10 (95% confidence interval: 1.07, 1.14); the random-effects estimate was similar. The separate fixed-effect risk ratios for smoking only before the first pregnancy (5 studies) or only after the first pregnancy (16 studies) were both 1.07, providing no evidence that breast tissue is more susceptible to malignant transformation from smoking before the first pregnancy. While these small summary risk ratios may represent causal effects, residual confounding could readily produce estimates of this size in the absence of any causal effect.

With case-parent triads, one can estimate genotype relative risks by measuring the apparent overtransmission of susceptibility genotypes from parents to affected offspring. Results obtained using such designs, properly analyzed, resist both bias due to population structure and bias due to self-selection. Most diseases are not purely genetic, and environmental cofactors can also be important. In this paper, the authors describe how a polytomous logistic regression method previously developed for studying genetic effects on a quantitative trait can be used with case-parent data to study multiplicative gene-by-environment interaction. The idea is that if the joint effect of exposure and genotype on risk is submultiplicative or supermultiplicative, then, conditional on the parental genotypes, inheritance of a susceptibility genotype by affected offspring will appear to have been influenced by the offspring's exposure level. The authors' approach tolerates exposure-complicated genetic population structure, and simulations suggest power and Type I error rates comparable to those of competitors. With this approach, one can estimate the usual interaction parameters under a much less stringent assumption than gene-environment independence in the source population. Incompletely genotyped triads can contribute through an expectation-maximization algorithm. To illustrate, the authors consider polymorphisms in detoxification pathway genes and maternal smoking in relation to the birth defect oral cleft.

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (1985-1993) recruited 29,133 Finnish male cigarette smokers, finding that vitamin E supplementation had no overall effect on mortality. The authors of this paper found that the effect of vitamin E on respiratory infections in ATBC Study participants was modified by age, smoking, and dietary vitamin C intake; therefore, they examined whether the effect of vitamin E supplementation on mortality is modified by the same variables. During a median follow-up time of 6.1 years, 3,571 deaths occurred. Age and dietary vitamin C intake had a second-order interaction with vitamin E supplementation of 50 mg/day. Among participants with a dietary vitamin C intake above the median of 90 mg/day, vitamin E increased mortality among those aged 50-62 years by 19% (95% confidence interval: 5, 35), whereas vitamin E decreased mortality among those aged 66-69 years by 41% (95% CI: -56, -21). Vitamin E had no effect on participants who had a dietary vitamin C intake below the median. Smoking quantity did not modify the effect of vitamin E. This study provides strong evidence that the effect of vitamin E supplementation on mortality varies between different population groups. Further study is needed to confirm this heterogeneity.

Cigarette smoking protects against preeclampsia but increases the risk of small-for-gestational-age birth (SGA). Regarding body weight, the converse is true: obesity elevates rates of preeclampsia but reduces rates of SGA. The authors assessed the combined effects of smoking and weight among US women developing preeclampsia or SGA, studying 7,757 healthy, primigravid women with singleton pregnancies in 1959-1965. Smoking (never, light, heavy), stratified by prepregnancy body mass index (BMI (weight (kg)/height (m)(2)); underweight, overweight, obese), was examined in relation to preeclampsia and SGA. Among underweight (BMI <18.5) and normal-weight (BMI 18.5-24.9) women, smoking decreased the risk of preeclampsia (for heavy smoking, light smoking, nonsmoking, test for trend p = 0.002 for underweight and p = 0.009 for normal weight) after adjustment for age, race, and socioeconomic status. However, among overweight/obese women (BMI >or=25), this trend was not apparent (p = 0.4). Among both underweight and overweight women, smoking significantly increased SGA risk (trend p < 0.001 for underweight and p = 0.02 for overweight/obese). Obesity eliminated the inverse association between smoking and preeclampsia but did not substantially alter the positive association between smoking and SGA. A possible unifying biologic explanation is discussed in this paper.

The authors examined the impact of smoking status on the relation between body mass index (weight (kg)/ height (m)2) and mortality across a group of 15 diverse observational studies. The studies included a heterogeneous sample of national samples, cohort studies with mortality follow-up, and clinical trials. Consideration of the data according to natural strata resulted in the formation of 42 analytic cohorts. The authors examined survival through the end of follow-up for each study, as influenced by body mass index, age, and current smoking status at baseline, using a proportional hazards model to describe the relation between body mass index and mortality with control for age and smoking status. In this paper, the authors demonstrate that the estimated body mass index of minimum mortality changes when data are analyzed while ignoring smoking status; but they also demonstrate through a simulation study that eliminating smokers from the data sets prior to analysis produces results similar to those expected from the elimination of numerically similar random proportions of the data sets prior to analysis. Based on the results of these analyses, the authors find no support for the commonly held practice of eliminating smokers from a data set prior to examining the body mass index-mortality relation.

Lung Health Study participants were smokers aged 35-60 years with mild lung function impairment who participated in a 5-year, 10-center (nine in the United States, one in Canada) clinical trial in 1986-1994. The authors compared the relation of randomized treatment assignments and of smoking history during the study with changes in lung function between men and women. Spirometry was performed annually, and 3,348 men and 1,998 women attended the follow-up clinic visit that included spirometry at year 5. This paper reports on an analysis of changes in lung function by gender, treatment group, and three smoking history categories: sustained quitters, intermittent quitters, and continuing smokers. Among participants who quit smoking in the first year, mean forced expiratory volume in 1 second (FEV1) expressed as a percentage of the predicted value of FEV1 given the person's age, height, gender, and race (FEV1%) increased more in women (3.7% of predicted) than in men (1.6% of predicted) (p < 0.001). Across the 5-year follow-up period, among sustained quitters, women gained more in FEV1% of predicted than did men. Methacholine reactivity was more strongly related to rates of decline in women than in men (p < 0.001). Therefore, among persons at risk for chronic obstructive pulmonary disease, smoking cessation has an even clearer advantage for women than it does for men. [ABSTRACT FROM AUTHOR]

In air pollution epidemiology, estimates of long term exposure are often based on measurements made at one fixed site monitor per area. This may lead to exposure misclassification. The present paper validates a questionnaire-based indicator of ambient air pollution levels and its applicability to assess their within-area variability. Within the framework of the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cross-sectional study (1991), 9,651 participants reported their level of annoyance caused by air pollution on an 11-point scale. This subjective measure was compared with annual mean concentrations of particulate matter less than 10 μm in diameter (PM10) and nitrogen dioxide. The impact of individual factors on reported scores was evaluated. Nitrogen dioxide concentrations at home outdoors (measured in 1993), smoking, workplace dust exposure, and respiratory symptoms were found to be predictors of individual annoyance scores. Regression of population mean annoyance scores against annual mean PM10 and nitrogen dioxide concentrations (measured in 1993 and 1991, respectively) across areas showed a linear relation and strong correlations (r > 0.85). Analysis within areas yielded consistent results. The observed associations between subjective and objective air pollution exposure estimates suggest that population mean scores, but not individual scores, may serve as a simple tool for grading air quality within areas. Reported annoyance due to air pollution should be considered an indicator for a complex environmental condition and thus might be used for evaluating the implementation of environmental policies. [ABSTRACT FROM PUBLISHER]

Infants born to mothers who smoke are a few hundred grams smaller, on average, than the infants of nonsmokers. This effect on fetal growth is regarded as evidence of the reproductive toxicity of cigarette smoking. In this paper, data from nearly 260,000 births in the state of Missouri (1980-1984) were analyzed using a method based on adjustment to relative birth weight. Two additional effects of smoking are demonstrated with this analysis; i.e., smokers are at higher risk of delivering very small preterm infants, and their infants have higher perinatal mortality at every relative birth weight. The latter is not apparent on an absolute birth weight scale and thus is not generally recognized. A supplementary analysis of births at high altitude is carried out to suggest that effects on fetal growth (whether from smoking or other factors) can occur independently of effects on mortality.

To determine the effects of 5 years of community-wide cardiovascular health education on smoking prevalence and cessation, the authors analyzed data from the Stanford Five-City Project, an experimental field study with two treatment cities and two control cities. Representative samples of the population aged 12-74 years were drawn at baseline and every 2 years thereafter to obtain four independent cross-sectional surveys; participants aged 25-74 years are included in this paper (n approximately 440 per city per survey; total n = 6,981). The baseline sample was asked to return to three follow-up surveys, also 2 years apart, and those that did (n = 805) constitute the cohort survey sample. Self-reported cigarette smoking was confirmed by plasma thiocyanate and expired-air carbon monoxide levels. Smoking prevalence decreased over time in all cities, but in the cohort the decrease tended to be greater in treatment than in control cities (p = 0.10, two-tailed); the treatment-control difference was consistent over time (-1.51 percentage points/year in treatment vs. -0.78 percentage points/year in control, p = 0.007, two-tailed). In contrast, smoking prevalence in the independent samples declined similarly in treatment and control cities, changes were not linear, and rates varied within cities between times. Baseline smokers in both the cohort and the follow-up independent surveys were significantly more likely to quit in the treatment cities than in the control cities.

This paper describes methods for simultaneous cross-sectional and longitudinal analysis of repeated measurements obtained in cohort studies with regular examination schedules, then uses these methods to describe age-related changes in pulmonary function level among nonsmoking participants in the Six Cities Study, a longitudinal study of air pollution and respiratory health conducted between 1974 and 1983 in Watertown, Massachusetts; Kingston and Harriman, Tennessee; St. Louis, Missouri; Steubenville, Ohio; Portage, Wisconsin; and Topeka, Kansas. The subjects, initially aged 25-74, were examined on three occasions at 3-year intervals. Individual rates of loss increased more rapidly with age than predicted from the cross-sectional model. For example, for a male of height 1.75 m, the cross-sectional model predicted an increase in the annual rate of loss of FEV1 from 23.7 ml/yr at age 25 to 39.0 ml/yr at age 75, while the longitudinal model gave rates of loss increasing from 12.9 ml/yr at age 25 to 58.2 ml/yr at age 75. These results contrast with those of other studies comparing longitudinal and cross-sectional estimates of pulmonary function loss.

This paper addresses two questions: 1) What is the relation of hemoglobin in the second gestational month to preterm birth and low birth weight? 2) How does the relation differ when hemoglobin in the fifth or eighth month or the lowest pregnancy hemoglobin are examined in place of first trimester values? These relations were examined prospectively in 829 women from Shanghai, China in 1991–1992. The population was nearly homogeneous by race, parity, antenatal care, and smoking. Rates of birth outcomes were compared between hemoglobin categories based on 10 g/liter groupings, with 110–119 g/liter as the reference group. Rates of low birth weight and preterm birth (but not small-for-gestational age) were related to early pregnancy hemoglobin concentration in a U-shaped manner. The relative risks (95% confidence intervals) for preterm birth in women by g/liter of hemoglobin were 2.52 (0.95–6.64) for ≥130 g/liter, 1.11 (0.41–2.99) for 120–129 g/liter, 1.64 (0.77–3.47) for 100–109 g/liter, 2.63 (1.17–5.90) for 90–99 g/liter, and 3.73 (1.36–10.23) for 60–89 g/liter. Use of hemoglobin values in the fifth or eighth month attenuated the association with preterm birth. When lowest pregnancy hemoglobin values were used, the association of anemia with both outcomes was obscured, and risk of preterm birth at high hemoglobin values increased dramatically. Am J Epidemiol 1998; 148: 998–1006. [ABSTRACT FROM AUTHOR]

A population-based case-control study of renal cell cancer was conducted in Minnesota between 1988 and 1990. it included 690 historically confirmed incident cases identified through the state cancer surveillance system, and 707 age and sex frequency-matched controls. In this paper, the authors present estimates of the proportion of renal cell cancer cases attributable (or population attributable risk (PAR)) to 1) well-established risk factors, namely smoking, excess weight, and hypertension, and 2) more speculative risk factors, namely elevated protein intake, history of renal disease (i.e., stone, injury, or infection) and high parity among women. These estimates were based on information obtained from directly interviewed subjects (65% of cases and 100% of controls). The PARs for the three main risk factors were 21 % for hypertension (defined by a reported personal history of hypertension or of treatment with antihypertensive or diuretic drugs), 21% for excess weight (defined by an elevation of the usual body mass index above the first quartile), and 18% for smoking (past and current). Overall, these three factors accounted for 49% of cases. The proportion increased to 60% when the three more speculative risk factors were considered as well. Sex-specific analyses revealed a greater impact of smoking among men mainly due to a higher prevalence of past smoking. In contrast, the impact of hypertension and excess weight was greater among women due to higher relative risks. These results suggest that 1) intervention measures aimed at reducing smoking, excess weight, and hypertension could substantially lower the overall incidence of renal cell cancer, and 2) intervention measures may have to be sex-specific. Conversely, because at least 40% of cases remain unexplained by the risk factors under study, further etiologic research is needed into renal cell cancer, an increasingly common form of cancer. Am J Epidemiol 1998; 148: 424–30. [ABSTRACT FROM AUTHOR]

In this paper, the authors model the nonmonotonic relation between body mass index (BMI) (weight (kg)/height2 (m2)) and mortality in 13,242 black and white participants in the NHANES I Epidemiologic Follow-up Study in order to estimate the BMI at which minimum mortality occurs. The BMI of minimum mortality was 27.1 for black men (95% confidence interval (Cl) 24.8–29.4), 26.8 for black women (95% CI 24.7–28.9), 24.8 for white men (95% CI 23.8–25.9), and 24.3 for white women (95% Cl 23.3–25.4). Each confidence interval included the group average. Analyses conducted by smoking status and after exclusion of persons with baseline illness and persons who died during the first 4 years of follow-up led to virtually identical estimates. The authors determined the range of values over which risk of all-cause mortality would increase no more than 20% in comparison with the minimum. This interval was nine BMI units wide, and it included 70% of the population. These results were confirmed by parallel analyses using quantiles. The model used allowed the estimation of parameters in the BMI-mortality relation. The resulting empirical findings from each of four race/sex groups, which are representative of the US population, demonstrate a wide range of BMIs consistent with minimum mortality and do not suggest that the optimal BMI is at the lower end of the distribution for any subgroup. Am J Epidemiol 1998;147:739–49. [ABSTRACT FROM PUBLISHER]

Epidemiology has a rich tradition in western New York State, beginning with the classic study by Austin Flint of a waterbome typhoid fever outbreak in North Boston in 1843. Other important investigations included the study of the Buffalo poliomyelitis epidemic of 1912, by Wade Hampton Frost, which provided a comprehensive characterization of the epidemiology of the disease, and the first case-control study of cigarette smoking and lung cancer, by Morton L. Levin et al., conducted at the Roswell Park Memorial Cancer Institute in the 1940s. Other studies carried out before 1960 arid included in the review deal with additional typhoid fever outbreaks, tuberculosis, breast cancer, and coronary heart disease. [ABSTRACT FROM AUTHOR]

Lower levels of plasma total cholesterol have been observed during severe infection, but it is not known whether the minor illnesses encountered in the general population are also associated with reduced cholesterol. This paper examines the relation between minor illness and plasma lipids, using 7- and 10-year follow-up data from more than 3,000 generally healthy participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. At both 7 and 10 years, approximately 8.5% of participants stated they had been “ill with cold, flu, fever, or vomiting in the past 24 hours.” In both cross-sectional and longitudinal analyses, the plasma total cholesterol was about 5 mg/dl lower (p < 0.006) and high density lipoprotein cholesterol about 1.2 mg/dl lower (p < 0.12) in those who reported minor illness than in those who did not. Plasma triglycerides did not vary with minor illness. The authors conclude that reductions in plasma total, low density, and high density lipoprotein cholesterol mark an acute phase response even during minor illness. These reductions may bias surveys over a limited geographic area during a short period because the proportion with minor illness may vary locally. Because this effect should be stronger with more precise illness diagnosis, clinicians should avoid making measurements for cholesterol management when illness may alter plasma lipid levels and the resulting decisions. [ABSTRACT FROM AUTHOR]

We describe a new method for presenting and interpreting linear trends in health inequalities, and present a proof-of-concept analysis of inequalities in smoking among adolescents in Europe. We estimated the regression line of the assumed linear relationship between smoking prevalence in low– and high–socioeconomic status (SES) youth over time. Using simulation, we constructed a 95% confidence interval (CI) for the smoking prevalence in low-SES youth for when this would be 0% in high-SES youth, and we calculated the likelihood of eradicating smoking inequality (<5% for both low and high SES). This method was applied to data on adolescents aged 15–16 years (n  = 250,326) from 23 European countries, derived from the 2003–2015 European Survey Project on Alcohol and Other Drugs. Smoking prevalence decreased more slowly among low- than among high-SES adolescents. The estimated smoking prevalence was 9.4% (95% CI: 6.1, 12.7) for boys and 5.4% (95% CI: 1.4, 9.2) for girls with low SES when 0% with high SES. The likelihood of eradicating smoking inequality was <1% for boys and 37% for girls. We conclude that this novel methodological approach to trends in health inequalities is feasible in practice. Applying it to trends in smoking inequalities among adolescents in Europe, we found that Europe is currently not on track to eradicate youth smoking across SES groups. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a paper by L. E. Beane Freeman which suggests that the inverse association between selenium and bladder cancer may be due to confounding by smoking.

Smoke-free housing policies are intended to reduce the deleterious health effects of secondhand smoke exposure, but there is limited evidence regarding their health impacts. We examined associations between implementation of a federal smoke-free housing rule by the New York City Housing Authority (NYCHA) and pediatric Medicaid claims for asthma, lower respiratory tract infections, and upper respiratory tract infections in the early post–policy intervention period. We used geocoded address data to match children living in tax lots with NYCHA buildings (exposed to the policy) to children living in lots with other subsidized housing (unexposed to the policy). We constructed longitudinal difference-in-differences models to assess relative changes in monthly rates of claims between November 1, 2015, and December 31, 2019 (the policy was introduced on July 30, 2018). We also examined effect modification by baseline age group (≤2, 3–6, or 7–15 years). In New York City, introduction of a smoke-free policy was not associated with lower rates of Medicaid claims for any outcomes in the early postpolicy period. Exposure to the smoke-free policy was associated with slightly higher than expected rates of outpatient upper respiratory tract infection claims (incidence rate ratio = 1.05, 95% confidence interval: 1.01, 1.08), a result most pronounced among children aged 3–6 years. Ongoing monitoring is essential to understanding long-term health impacts of smoke-free housing policies. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and 3-part meta-analysis to characterize the relationship between smoking and perinatal death, defined as the combination of stillbirth and neonatal death. The PubMed database was searched (1956-August 31, 2011) with keywords, and manual reference searches of included articles and Surgeon Generals' reports were conducted. The full texts of 1,713 articles were reviewed, and 142 articles that examined the associations between active or passive smoking and perinatal death were included in themeta-analyses. Datawere abstracted by 2 reviewers. Any active maternal smoking was associated with increased risks of stillbirth (summary relative risk (sRR) = 1.46, 95% confidence interval (CI): 1.38, 1.54 (n = 57 studies)), neonatal death (sRR = 1.22, 95% CI: 1.14, 1.30 (n = 28)), and perinatal death (sRR = 1.33, 95% CI: 1.25, 1.41 (n = 46)). The risks of stillbirth, neonatal death, and perinatal death increased with the amount smoked by the mother. Biases in study publication, design, and analysis were present but did not significantly affect the results. These findings strengthen the evidence that women should not smoke while pregnant, and all women of reproductive age should be warned that smoking increases the risks of stillbirth, neonatal death, and perinatal death. [ABSTRACT FROM AUTHOR]

In this article, I provide a perspective on the tobacco epidemic and epidemiology, describing the impact of the tobacco-caused disease epidemic on the field of epidemiology. Although there is an enormous body of epidemiologic evidence on the associations of smoking with health, little systematic attention has been given to how decades of research have affected epidemiology and its practice. I address the many advances that resulted from epidemiologic research on smoking and health, such as demonstration of the utility of observational designs and important parameters (the odds ratio and the population attributable risk), guidelines for causal inference, and systematic review approaches. I also cover unintended and adverse consequences for the field, including the strategy of doubt creation and the recruitment of epidemiologists by the tobacco industry to serve its mission. The paradigm of evidence-based action for addressing noncommunicable diseases began with the need to address the epidemic of tobacco-caused disease, an imperative for action documented by epidemiologic research. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999–2017) on 1,120 premenopausal women from the Study of Women's Health Across the Nation (SWAN). Causal mediation analysis was applied to quantify the degree to which follicle-stimulating hormone (FSH) and estradiol levels could mediate the associations between PFAS and incident natural menopause. Participants with higher PFAS concentrations had shorter times to natural menopause, with a relative survival of 0.82 (95% confidence interval (CI): 0.69, 0.96) for linear perfluorooctane sulfonate (n-PFOS), 0.84 (95% CI: 0.69, 1.00) for sum of branched-chain perfluorooctane sulfonate (Sm-PFOS), 0.79 (95% CI: 0.66, 0.93) for linear-chain perfluorooctanoate (n-PFOA), and 0.84 (95% CI: 0.71, 0.97) for perfluorononanoate (PFNA), comparing the highest tertile of PFAS concentrations with the lowest. The proportion of the effect mediated through FSH was 8.5% (95% CI: −11.7, 24.0) for n-PFOS, 13.2% (95% CI: 0.0, 24.5) for Sm-PFOS, 26.9% (95% CI: 15.6, 38.4) for n-PFOA, and 21.7% (6.8, 37.0) for PFNA. No significant mediation by estradiol was observed. The effect of PFAS on natural menopause may be partially explained by variations in FSH concentrations. [ABSTRACT FROM AUTHOR]

In the analysis of observational studies, inverse probability weighting (IPW) is commonly used to consistently estimate the average treatment effect (ATE) or the average treatment effect in the treated (ATT). The variance of the IPW ATE estimator is often estimated by assuming that the weights are known and then using the so-called "robust" (Huber-White) sandwich estimator, which results in conservative standard errors (SEs). Here we show that using such an approach when estimating the variance of the IPW ATT estimator does not necessarily result in conservative SE estimates. That is, assuming the weights are known, the robust sandwich estimator may be either conservative or anticonservative. Thus, confidence intervals for the ATT using the robust SE estimate will not be valid, in general. Instead, stacked estimating equations which account for the weight estimation can be used to compute a consistent, closed-form variance estimator for the IPW ATT estimator. The 2 variance estimators are compared via simulation studies and in a data analysis of the association between smoking and gene expression. [ABSTRACT FROM AUTHOR]

The precise quantitation of smoking during pregnancy is difficult in retrospective studies. Routinely collected blood specimens from newborns, stored as dried blood spots, may provide a low-cost method to objectively measure maternal smoking close to the time of delivery. This article compares cotinine levels in dried blood spots to those in umbilical cord blood to assess cotinine in dried blood spots as a biomarker of maternal smoking close to the time of delivery. The California Genetic Disease Screening Program provided dried blood spots from 428 newborns delivered in 2001–2003 with known umbilical cord blood cotinine levels. Cotinine in dried blood spots was measured in 6.35­-mm punches by using liquid chromatography­–tandem mass spectrometry (quantitation limit, 3.1 ng/mL). Repeated measures of cotinine in dried blood spots were highly correlated (R2 = 0.99, P < 0.001) among 100 dried blood spots with cotinine quantitated in 2 separate punches. Linear regression revealed that cotinine levels in dried blood spots were slightly lower than those in umbilical cord blood and predicted umbilical cord blood cotinine levels well (β = 0.95, R2 = 0.80, and P < 0.001 for both cotinine levels in log10 scale). When defining active smoking as a cotinine level of 10 ng/mL or more and using umbilical cord blood cotinine as the criterion standard, we found that measurements of cotinine in dried blood spots had high sensitivity (92.3%) and specificity (99.7%) in the prediction of maternal active smoking. Cotinine levels in dried blood spots are an accurate biomarker of maternal smoking close to the time of delivery. [ABSTRACT FROM PUBLISHER]

Increased perinatal mortality among smokers' babies has been observed in many but not in all studies, with a statistically significant difference in some. This paper explores the hypothesis that maternal smoking may interact with other risk factors, so that a dose-related increase in perinatal mortality may be enhance or masked depending upon the presence or absence of these factors. Data are from the Ontario Perinatal Mortality Study of all single b irths in 10 teaching hospitals in Ontario in 1960-1961 a total of 51,490 births, including 701 fetal deaths and 655 early neonatal deaths. Perinatal mortality increased significantly with smoking, and was also affected by such factors as maternal age, parity, hospital status, previous pregnancy history, hemoglobin level, and others. Smoking frequencies also varied by many of these characteristics. Perinatal mortality was therefore analyzed by the amount smoked during pregnancy within subgroups of these antecedent risk factors. When smoking and other risk factors were cross-tabulated among 52 data subgroups, only the light smokers (less than 1 pack per day) under age 20 had lower perinatal mortality rates than their nonsmoking counterparts. In almost all subgroups the mortality increase with smoking was dose-related, but not in a simple, linear way. The increased risk of perinatal mortality associated with light smoking among young, low-parity, non-anemic mothers was less than 10 percent. At the other extreme, mothers of high parity, public hospital status, with previous low birthweight births, or with hemoglobin less than 11 gm had increased perinatal mortality risks of 70-100 percent when they were heavy smokers. The failure of some studies to find a significant increase in perinatal mortality with maternal smoking may be due to selection of study populations from the end of the spectrum where light smoking is associated with only a slight increase in perinatal risk. Other studies may select higher risk populations, where the influence of smoking on mortality is stronger. Depending on the magnitude of the difference, the amount smoked, and the size of the study, results might or might not be statistically significant.

This paper examines changes with time of mortality from lung cancer in Italy during the years 1950-1979 in relation to changes in smoking habits since 1900. In both sexes and for all ages mortality rose throughout this period, although for women the rates and the relative increases per year have been consistently much lower than for men. Between 1950-1952 and 1977-1979 the age-adjusted death rate per 100,000 men rose almost five times (from 10.01 to 49.55) whereas that for women only doubled (from 2.65 to 5.74), so that the male/female ratio increased from 3.78 to 8.65. In men successive cohorts show an increase of age-specific death rate, but there are indications that for men born after 1925 the mortality rate is beginning to level off. In women over 50 years of age mortality continues to rise, but below this age it tends to level off and decline. Analysis of the consumption of different types of tobacco products since 1900 suggests that the trends of mortality with time in different birth cohorts are explicable in terms of changes of use of cigarettes.

Both smoking and exposure to cotton textile dust have been associated with the development of chronic obstructive lung disease. The relative importance of these two effects are examined in this paper. This investigation is based on a cross-sectional study of white active and retire cotton textile workers 45 years and older seen in 1973 in Columbia, South Carolina with an average of 35 years worked in the mills. A questionnaire was completed and an expiratory flow volume curve obtained for each worker studied. Standard pulmonary function parameters including the forced vital capacity (FVC), the forced expired volume in one second (FEV1), and the maximum expiratory flow at 50% (MEF50%), and at 25% (MEF25%) were recorded. White residents 45 years and older from three communities studied from 1972 to 1974 were used as controls. A two-way analysis of variance examined both the effects of cotton dust and smoking on lung function. Both exposures significantly influenced lung function and were found to be additive and often equally important. When one effect was more important than the other, it was in FVC and FEV1 for cotton dust and in MEF50% and MEF25% for smoking.

The POLA (Pathologies Oculaires Liées à l'Age) Study is a population-based study of cataract and age-related macular degeneration and their risk factors being carried out among 2,584 residents of Sète, southern France, aged 60–95 years. Recruitment took place between June 1995 and July 1997. Cataract classification was based on a standardized lens examination by slit lamp, according to Lens Opacities Classification System III. This paper presents results obtained from cross-sectional analysis of the first phase of the study. In polytomous logistic regression analyses, an increased risk of cataract was found for female sex (cataract surgery: odds ratio (OR) = 3.03; cortical cataract: OR = 1.67), brown irises (cortical, nuclear, and mixed cataracts: OR = 1.61), smoking (cataract surgery: OR = 2.34 for current smokers and OR = 3.75 for former smokers), known diabetes of 10 or more years' duration (posterior subcapsular, cortical, and mixed cataracts and cataract surgery: OR = 2.72), use of oral corticosteroids for at least 5 years (posterior subcapsular cataract: OR = 3.25), asthma or chronic bronchitis (cataract surgery: OR = 2.04), cancer (posterior subcapsular cataract: OR = 1.92), and cardiovascular disease (cortical cataract: OR = 1.96). Decreased risk of cataract was found with higher education (all types of cataract and cataract surgery: OR = 0.59), hypertension (cataract surgery: OR = 0.57), and high plasma retinol levels (nuclear and mixed cataracts and cataract surgery: OR = 0.75 for a 1-standard-deviation increase). Most of the risk factors identified in this study confirm the findings of other studies. The association of cataract with plasma retinol level requires further investigation. Am J Epidemiol 2000;151:497–504. [ABSTRACT FROM PUBLISHER]

The authors examined the impact of smoking status on the relation between body mass index (weight (kg)/height (m)2) and mortality across a group of 15 diverse observational studies. The studies included a heterogeneous sample of national samples, cohort studies with mortality follow-up, and clinical trials. Consideration of the data according to natural strata resulted in the formation of 42 analytic cohorts. The authors examined survival through the end of follow-up for each study, as influenced by body mass index, age, and current smoking status at baseline, using a proportional hazards model to describe the relation between body mass index and mortality with control for age and smoking status. In this paper, the authors demonstrate that the estimated body mass index of minimum mortality changes when data are analyzed while ignoring smoking status; but they also demonstrate through a simulation study that eliminating smokers from the data sets prior to analysis produces results similar to those expected from the elimination of numerically similar random proportions of the data sets prior to analysis. Based on the results of these analyses, the authors find no support for the commonly held practice of eliminating smokers from a data set prior to examining the body mass index-mortality relation. Am J Epidemiol 1999;150: 1297-308. [ABSTRACT FROM PUBLISHER]

Morbidity and mortality have been increasing among middle-aged and young-old Americans since the turn of the century. We investigated whether these unfavorable trends extend to younger cohorts and their underlying physiological, psychological, and behavioral mechanisms. Applying generalized linear mixed-effects models to data from 62,833 adults from the National Health and Nutrition Examination Surveys (1988–2016) and 625,221 adults from the National Health Interview Surveys (1997–2018), we found that for all sex and racial groups, physiological dysregulation has increased continuously from Baby Boomers through late-Generation X and Generation Y. The magnitude of the increase was higher for White men than for other groups, while Black men had a steepest increase in low urinary albumin (a marker of chronic inflammation). In addition, Whites underwent distinctive increases in anxiety, depression, and heavy drinking, and they had a higher level than Blacks and Hispanics of smoking and drug use in recent cohorts. Smoking is not responsible for the increasing physiological dysregulation across cohorts. The obesity epidemic contributes to the increase in metabolic syndrome but not in low urinary albumin. The worsening physiological and mental health profiles among younger generations imply a challenging morbidity and mortality prospect for the United States, one that might be particularly inauspicious for Whites. [ABSTRACT FROM AUTHOR]

There are few if any reports regarding the role of lifetime waterpipe smoking in the etiology of multiple sclerosis (MS). In a population-based incident case-control study conducted in Tehran, Iran, we investigated the association between waterpipe smoking and MS, adjusted for confounders. Cases (n  = 547) were patients aged 15–50 years identified from the Iranian Multiple Sclerosis Society between 2013 and 2015. Population-based controls (n  = 1,057) were persons aged 15–50 years recruited through random digit telephone dialing. A doubly robust estimation method, the targeted maximum likelihood estimator (TMLE), was used to estimate the marginal risk ratio and odds ratio for the association between waterpipe smoking and MS. The estimated risk ratio and odds ratio were both 1.70 (95% confidence interval: 1.34, 2.17). The population attributable fraction was 21.4% (95% confidence interval: 4.0, 38.8). Subject to the limitations of case-control studies in interpreting associations causally, these results suggest that waterpipe use, or strongly related but undetermined factors, increases the risk of MS. Further epidemiologic studies, including nested case-control studies, are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

From 1965 to 1990, the prevalence of cigarette smoking among US adults (aged 18 years) fell steadily and substantially. Data for the 1990s suggest that the smoking initiation rate is increasing and that the decline in the prevalence of smoking may have stalled, raising the fear that the historical 25-year decline will not continue. The authors used a new dynamic forecasting model to show that although the decline may slow down, the demographics of smoking imply that prevalence will inexorably continue to decline over the next several decades, even without any intensified efforts aimed at tobacco control. The authors estimated and validated the model using historical (1965–1993) data collected by the National Health Interview Surveys on the prevalence of smoking among adults. Their results indicate that the current increase in the smoking initiation rate partially explains the fact that the prevalence of smoking has apparently leveled off, but even if the most grim assumptions about future initiation rates are used, the prevalence of smoking among adults will continue to decline for several more decades. The authors predict that if current initiation and cessation behaviors persist, the prevalence of smoking among adults will automatically decline from its current level of 25% to 15–16% by the second quarter of the next century. Even so, smoking will remain the nation's leading cause of premature death. Am J Epidemiol 1998;148:249–58. [ABSTRACT FROM AUTHOR]

The article focuses on the association of cigarette smoking with lung cancer in developed countries. It mentions that public health policy is based on legislative measures, related to the involvement of medical and scientific leadership. It mentions that smoking cause cancer in men and women and influenced the diseases including myocardial infarction and emphysema.

The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45–75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993–1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts. [ABSTRACT FROM AUTHOR]

To investigate the risk of lung cancer after exposure to welding fumes, hexavalent chromium (Cr(VI)), and nickel, we analyzed 3,418 lung cancer cases and 3,488 controls among men from 2 German case-control studies (1988–1996). We developed a welding-process exposure matrix from measurements of these agents, and this was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals conditional on study, and they adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welders. Odds ratios for lung cancer with high exposure were 1.55 (95% confidence interval (CI): 1.17, 2.05; median, 1.8 mg/m3 × years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 μg/m3 × years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 μg/m3 × years) for nickel. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration for Cr(VI) and nickel. Our results showed that welding fumes, Cr(VI), and nickel might contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging. [ABSTRACT FROM AUTHOR]

Cigarette smoking protects against preeclampsia but increases the risk of small-for-gestational-age birth (SGA). Regarding body weight, the converse is true: obesity elevates rates of preeclampsia but reduces rates of SGA. The authors assessed the combined effects of smoking and weight among US women developing preeclampsia or SGA, studying 7,757 healthy, primigravid women with singleton pregnancies in 1959–1965. Smoking (never, light, heavy), stratified by prepregnancy body mass index (BMI (weight (kg)/height (m)2); underweight, overweight, obese), was examined in relation to preeclampsia and SGA. Among underweight (BMI p = 0.002 for underweight and p = 0.009 for normal weight) after adjustment for age, race, and socioeconomic status. However, among overweight/obese women (BMI ≥25), this trend was not apparent (p = 0.4). Among both underweight and overweight women, smoking significantly increased SGA risk (trend p p = 0.02 for overweight/obese). Obesity eliminated the inverse association between smoking and preeclampsia but did not substantially alter the positive association between smoking and SGA. A possible unifying biologic explanation is discussed in this paper. [ABSTRACT FROM AUTHOR]

Life satisfaction is increasingly recognized as an important determinant of health; however, prospective population-based studies on this topic are limited. We estimated the risk of chronic disease and death according to life satisfaction among a population-based cohort in Ontario, Canada (n = 73,904). The cohort included 3 pooled cycles of the Canadian Community Health Survey (2003–2008) linked to 6 years of follow-up (to 2015), using population-based health databases and validated disease-specific registries. The databases capture incident and prevalent cases of diabetes, cancer, chronic obstructive pulmonary disease, heart disease, and death. Multivariable Cox proportional hazard models were used to estimate hazards of incident chronic disease and death, and were adjusted for sociodemographic, behavioral, and clinical confounders, including age, sex, comorbidity, mood disorder, smoking, alcohol consumption, physical activity, body mass index, immigrant status, education, and income. In the fully adjusted models, risk of both death and incident chronic disease was highest for those most dissatisfied with life (for mortality, hazard ratio = 1.59, 95% confidence interval: 1.15, 2.19; for chronic disease, hazard ratio = 1.70, 95% confidence interval: 1.16, 2.51). In this population-based cohort, poor life satisfaction was an independent risk factor for incident chronic disease and death, supporting the idea that interventions and programs that improve life satisfaction will affect population health. [ABSTRACT FROM AUTHOR]

A substantial body of literature has shown robust associations between prenatal smoking exposure and DNA methylation levels. The pattern of DNA methylation can be used as a molecular signature of past prenatal smoking exposure and might also provide mechanistic insights into associations between prenatal smoking exposure and adverse health outcomes. In this issue of the Journal , Cardenas et al. (Am J Epidemiol. 2019;188(11):1878–1886) evaluated whether DNA methylation mediates the association between prenatal smoking and low birth weight in a tissue that is mechanistically relevant to birth weight—the placenta—using formal mediation analyses. They found that methylation levels, at 5 loci, mediated smoking exposure effects on birth weight but only among children whose mothers smoked during pregnancy. Given the use of formal mediation methods and measurement in a mechanistically relevant tissue, this work has the potential to inform novel directions for intervention. Replication of these findings in larger and more racially and ethnically diverse samples, repeated measures to better tease apart the timing of DNA methylation changes with respect to exposure and birth weight, and continued use of intervention-focused mediation methods are needed before the impact of these findings will be fully realized. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Morton Levin (1904-1995): History in the Making," by Haroutune K. Armenian and Moyses Szklo in a previous issue of the journal.

A letter to the editor is presented in response to the article "Family History of Cancer and Risk of Lung Cancer Among Lifetime Nonsmoking Women in the United States," by Wu AH and colleagues in a previous issue of the journal.

The Journal is notified by Drs. Jaume Marrugat and Roberto Elosua of two errors in table 5 of their recently published paper (1).The authors point out that in the published version of table 5, the β coefficients for VO2max and for the constant are misaligned. In the published table, the row of β coefficients for VO2max appears incorrectly opposite the caption ‘EEPA (100 kcal/day)’ but should have appeared one line above this, opposite ‘V02max (ml/kg/minute).’ Similarly, the published table shows the row of B coefficients for the constant incorrectly opposite ‘(yes = 1/no = 0)’ under “Current smoking” instead of one line lower, opposite ‘Constant.’The authors and the Journal regret these errors. [ABSTRACT FROM AUTHOR]

The US Great Recession resulted in an alarming number of home foreclosures that weakened the social and physical environment of thousands of neighborhoods. Few studies have evaluated whether these neighborhood changes were related to changes in individual behaviors. We examined the relationship between changes in neighborhood-level home foreclosure within a quarter-mile (0.4-km) buffer of the residence and changes in cigarette smoking and alcohol use among 3,807 adults enrolled in the Multi-Ethnic Study of Atherosclerosis during 2005–2012, using econometric individual-level fixed-effects models. Increases in neighborhood-level foreclosure were associated with small decreases in the number of cigarettes smoked per day (mean difference = −0.08, 95% confidence interval: −0.11, −0.04) and small increases in the number of alcoholic beverages consumed per week (mean difference = 0.11, 95% confidence interval: 0.05, 0.17). Neighborhood-level foreclosure may not uniformly influence high-risk behaviors. The impact of home foreclosure on adult drinking should be further explored, given its potentially negative implications for health. [ABSTRACT FROM AUTHOR]

There may be sex differences in the response to nicotine, according to findings of studies in animals; however, sex differences in the natural course of cigarette smoking and nicotine dependence are documented in few studies. Prevalent (n = 240 girls; n = 184 boys) and incident (n = 231 girls; n = 184 boys) cigarette smokers from the Nicotine Dependence in Teens Study were followed up to 5 years after first puff, from age 12 to 18 years (1999–2005). We used Cox proportional hazards models to compare time to development of 3 cigarette-use (i.e., whole cigarette; 100 cigarettes lifetime; regular smoking), and 3 nicotine-dependence symptom (i.e., “really need a cigarette”; mentally addicted; physically addicted) milestones across sex. Girls were at higher risk than boys of attaining all milestones; hazard ratios (95% confidence intervals) ranged from 1.35 (1.06, 1.72) for 100 cigarettes lifetime to 1.74 (1.44, 2.10) for “really need a cigarette.” Among nonregular smokers, 26% (8%; 43%) and 25% (6%; 44%) more girls than boys reported “really need a cigarette” 1 and 2 years, respectively, after first puff. Preventive interventions may need adjustment to incorporate these findings. Additional research should clarify the relative contribution of biological and social underpinnings of these sex differences. [ABSTRACT FROM AUTHOR]